A polypeptide possessing anti-insulin property was isolated from the urine of patients with lipoatrophic diabetes and proteinuric diabetic patients without lipoatrophy. It was not found in the urine of normal people or polypetide was also obtained from pituitaries of beef, hog, sheep and humans. The substance from all above sources has an isoelectric point of pH 4.1 and was shown to be capable of inducing hyperglycemia and insulin resistance in man and dogs. Its anti-insulin property was also demonstrated in vitro. Present studies indicate that the source of the urinary diabetogenic polypeptide is the pituitary gland. The molecular weight of the urinary polypeptide from proteinuric diabetic patients is 21,600 and that from human pituitaries is 20,600. Its diabetogenic potency is much greater than that of human growth hormone. The substance has now been purified. Development of a radioimmunoassay for the polypeptide is now in progress.